Circadian Modulation of the Cl(-) Equilibrium Potential in the Rat Suprachiasmatic Nuclei

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2014 Jun 21

PMID 24949446

Citations 21

Authors

Javier Alamilla

Azucena Perez-Burgos

Daniel Quinto

Raul Aguilar-Roblero

Affiliations

Soon will be listed here.

Abstract

The suprachiasmatic nuclei (SCN) constitute a circadian clock in mammals, where γ-amino-butyric acid (GABA) neurotransmission prevails and participates in different aspects of circadian regulation. Evidence suggests that GABA has an excitatory function in the SCN in addition to its typical inhibitory role. To examine this possibility further, we determined the equilibrium potential of GABAergic postsynaptic currents (E(GABA)) at different times of the day and in different regions of the SCN, using either perforated or whole cell patch clamp. Our results indicate that during the day most neurons in the dorsal SCN have an E(GABA) close to -30 mV while in the ventral SCN they have an E(GABA) close to -60 mV; this difference reverses during the night, in the dorsal SCN neurons have an E(GABA) of -60 mV and in the ventral SCN they have an E(GABA) of -30 mV. The depolarized equilibrium potential can be attributed to the activity of the Na(+)-K(+)-2Cl(-) (NKCC) cotransporter since the equilibrium potential becomes more negative following addition of the NKCC blocker bumetanide. Our results suggest an excitatory role for GABA in the SCN and further indicate both time (day versus night) and regional (dorsal versus ventral) modulation of E(GABA) in the SCN.

Citing Articles

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References

Wagner S, Sagiv N, Yarom Y . GABA-induced current and circadian regulation of chloride in neurones of the rat suprachiasmatic nucleus. J Physiol. 2001; 537(Pt 3):853-69. PMC: 2279012. DOI: 10.1111/j.1469-7793.2001.00853.x. View

Irwin R, Allen C . GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus network. Eur J Neurosci. 2009; 30(8):1462-75. PMC: 3700401. DOI: 10.1111/j.1460-9568.2009.06944.x. View

LeSauter J, Kriegsfeld L, Hon J, Silver R . Calbindin-D(28K) cells selectively contact intra-SCN neurons. Neuroscience. 2002; 111(3):575-85. PMC: 3296561. DOI: 10.1016/s0306-4522(01)00604-2. View

Abrahamson E, Moore R . Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res. 2001; 916(1-2):172-91. DOI: 10.1016/s0006-8993(01)02890-6. View

Castel M, Morris J . Morphological heterogeneity of the GABAergic network in the suprachiasmatic nucleus, the brain's circadian pacemaker. J Anat. 2000; 196 ( Pt 1):1-13. PMC: 1468035. DOI: 10.1046/j.1469-7580.2000.19610001.x. View

Itri J, Colwell C . Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus. J Neurophysiol. 2003; 90(3):1589-97. DOI: 10.1152/jn.00332.2003. View

Gribkoff V, Pieschl R, Wisialowski T, Park W, Strecker G, de Jeu M . A reexamination of the role of GABA in the mammalian suprachiasmatic nucleus. J Biol Rhythms. 1999; 14(2):126-30. DOI: 10.1177/074873099129000515. View

Belenky M, Sollars P, Mount D, Alper S, Yarom Y, Pickard G . Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus. Neuroscience. 2009; 165(4):1519-37. PMC: 2815043. DOI: 10.1016/j.neuroscience.2009.11.040. View

Gillespie C, Mintz E, Marvel C, Huhman K, Albers H . GABA(A) and GABA(B) agonists and antagonists alter the phase-shifting effects of light when microinjected into the suprachiasmatic region. Brain Res. 1997; 759(2):181-9. DOI: 10.1016/s0006-8993(97)00235-7. View

10.

Aguilar-Roblero R, Mercado C, Alamilla J, Laville A, Diaz-Munoz M . Ryanodine receptor Ca2+-release channels are an output pathway for the circadian clock in the rat suprachiasmatic nuclei. Eur J Neurosci. 2007; 26(3):575-82. DOI: 10.1111/j.1460-9568.2007.05679.x. View

11.

Kononenko N, Dudek F . Mechanism of irregular firing of suprachiasmatic nucleus neurons in rat hypothalamic slices. J Neurophysiol. 2004; 91(1):267-73. DOI: 10.1152/jn.00314.2003. View

12.

Liu C, Reppert S . GABA synchronizes clock cells within the suprachiasmatic circadian clock. Neuron. 2000; 25(1):123-8. DOI: 10.1016/s0896-6273(00)80876-4. View

13.

de Jeu M, Pennartz C . Circadian modulation of GABA function in the rat suprachiasmatic nucleus: excitatory effects during the night phase. J Neurophysiol. 2002; 87(2):834-44. DOI: 10.1152/jn.00241.2001. View

14.

Aguilar-Roblero R, Rodriguez C, Mendez-Franco J, Moran J, de la Mora M . Circadian rhythmicity in the GABAergic system in the suprachiasmatic nuclei of the rat. Neurosci Lett. 1993; 157(2):199-202. DOI: 10.1016/0304-3940(93)90736-5. View

15.

Ben-Ari Y . Excitatory actions of gaba during development: the nature of the nurture. Nat Rev Neurosci. 2002; 3(9):728-39. DOI: 10.1038/nrn920. View

16.

Reppert S, Weaver D . Coordination of circadian timing in mammals. Nature. 2002; 418(6901):935-41. DOI: 10.1038/nature00965. View

17.

Shimura M, Akaike N, Harata N . Circadian rhythm in intracellular Cl(-) activity of acutely dissociated neurons of suprachiasmatic nucleus. Am J Physiol Cell Physiol. 2002; 282(2):C366-73. DOI: 10.1152/ajpcell.00187.2000. View

18.

Morin L, Shivers K, Blanchard J, Muscat L . Complex organization of mouse and rat suprachiasmatic nucleus. Neuroscience. 2005; 137(4):1285-97. DOI: 10.1016/j.neuroscience.2005.10.030. View

19.

Shirakawa T, Honma S, Katsuno Y, Oguchi H, Honma K . Synchronization of circadian firing rhythms in cultured rat suprachiasmatic neurons. Eur J Neurosci. 2000; 12(8):2833-8. DOI: 10.1046/j.1460-9568.2000.00170.x. View

20.

Wagner S, Castel M, Gainer H, Yarom Y . GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity. Nature. 1997; 387(6633):598-603. DOI: 10.1038/42468. View